In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives
This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-06-01
|
| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/6/1755 |
| _version_ | 1797593051047133184 |
|---|---|
| author | Amr Selim Abu Lila Mohammed Amran Mohamed A. Tantawy Ehssan H. Moglad Shadeed Gad Hadil Faris Alotaibi Ahmad J. Obaidullah El-Sayed Khafagy |
| author_facet | Amr Selim Abu Lila Mohammed Amran Mohamed A. Tantawy Ehssan H. Moglad Shadeed Gad Hadil Faris Alotaibi Ahmad J. Obaidullah El-Sayed Khafagy |
| author_sort | Amr Selim Abu Lila |
| collection | DOAJ |
| description | This study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC<sub>50</sub> value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site. |
| first_indexed | 2024-03-11T02:02:03Z |
| format | Article |
| id | doaj.art-7216a9025034410095fb42ac382d4375 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T02:02:03Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7216a9025034410095fb42ac382d43752023-11-18T12:06:03ZengMDPI AGPharmaceutics1999-49232023-06-01156175510.3390/pharmaceutics15061755In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine DerivativesAmr Selim Abu Lila0Mohammed Amran1Mohamed A. Tantawy2Ehssan H. Moglad3Shadeed Gad4Hadil Faris Alotaibi5Ahmad J. Obaidullah6El-Sayed Khafagy7Department of Pharmaceutics, College of Pharmacy, University of Hail, Hail 81442, Saudi ArabiaDepartment of Pharmacy, Faculty of Health Sciences, Thamar University, Thamar 87246, YemenHormones Department, Medical Research and Clinical Studies Institute, National Research Centre, Dokki, Giza 12622, EgyptDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdul Rahman University, Riyadh 11671, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi ArabiaThis study demonstrates high drug-loading of novel pyridine derivatives (S1–S4) in lipid- and polymer-based core–shell nanocapsules (LPNCs) for boosting the anticancer efficiency and alleviating toxicity of these novel pyridine derivatives. The nanocapsules were fabricated using a nanoprecipitation technique and characterized for particle size, surface morphology, and entrapment efficiency. The prepared nanocapsules exhibited a particle size ranging from 185.0 ± 17.4 to 223.0 ± 15.3 nm and a drug entrapment of >90%. The microscopic evaluation demonstrated spherical-shaped nanocapsules with distinct core–shell structures. The in vitro release study depicted a biphasic and sustained release pattern of test compounds from the nanocapsules. In addition, it was obvious from the cytotoxicity studies that the nanocapsules showed superior cytotoxicity against both MCF-7 and A549 cancer cell lines, as manifested by a significant decrease in the IC<sub>50</sub> value compared to free test compounds. The in vivo antitumor efficacy of the optimized nanocapsule formulation (S4-loaded LPNCs) was investigated in an Ehrlich ascites carcinoma (EAC) solid tumor-bearing mice model. Interestingly, the entrapment of the test compound (S4) within LPNCs remarkably triggered superior tumor growth inhibition when compared with either free S4 or the standard anticancer drug 5-fluorouracil. Such enhanced in vivo antitumor activity was accompanied by a remarkable increase in animal life span. Furthermore, the S4-loaded LPNC formulation was tolerated well by treated animals, as evidenced by the absence of any signs of acute toxicity or alterations in biochemical markers of liver and kidney functions. Collectively, our findings clearly underscore the therapeutic potential of S4-loaded LPNCs over free S4 in conquering EAC solid tumors, presumably via granting efficient delivery of adequate concentrations of the entrapped drug to the target site.https://www.mdpi.com/1999-4923/15/6/1755antitumor activityEhrlich ascites carcinomaMTT assaynanocapsulepyridine derivatives |
| spellingShingle | Amr Selim Abu Lila Mohammed Amran Mohamed A. Tantawy Ehssan H. Moglad Shadeed Gad Hadil Faris Alotaibi Ahmad J. Obaidullah El-Sayed Khafagy In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives Pharmaceutics antitumor activity Ehrlich ascites carcinoma MTT assay nanocapsule pyridine derivatives |
| title | In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives |
| title_full | In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives |
| title_fullStr | In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives |
| title_full_unstemmed | In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives |
| title_short | In Vitro Cytotoxicity and In Vivo Antitumor Activity of Lipid Nanocapsules Loaded with Novel Pyridine Derivatives |
| title_sort | in vitro cytotoxicity and in vivo antitumor activity of lipid nanocapsules loaded with novel pyridine derivatives |
| topic | antitumor activity Ehrlich ascites carcinoma MTT assay nanocapsule pyridine derivatives |
| url | https://www.mdpi.com/1999-4923/15/6/1755 |
| work_keys_str_mv | AT amrselimabulila invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT mohammedamran invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT mohamedatantawy invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT ehssanhmoglad invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT shadeedgad invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT hadilfarisalotaibi invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT ahmadjobaidullah invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives AT elsayedkhafagy invitrocytotoxicityandinvivoantitumoractivityoflipidnanocapsulesloadedwithnovelpyridinederivatives |